DISCUSSION
LVA studied by EAM of atrial bipolar endocardial signals have been
recently established as a way to invasively define AF substrate. As an
advantage, it does not require additional approaches or catheters and
does not pose an additional risk to patients who, due to clinical
criteria, undergo this therapeutic approach. Most authors consider these
LVA as a surrogate of fibrosis13,14. Currently, we do
not have a clear validation of a threshold that we have to consider as
fibrosis. Some authors have adopted a statistical approach, considering
the 5th percentile of all mapping points as a threshold for abnormal
tissue. For example, Kapa and collaborators15proposed
a threshold of <0.2 mV for atrial fibrosis in posterior wall
and in the area between PV and left atrium, and <0.45mV for
the rest of the atrium, based on mapping of 20 patients with paroxysmal
AF, 10 of them with previous PV isolation. Another
study16 was carried out in patients with left
accessory pathway ablation, some of them with additional AF. In patients
without AF, 95% of electrograms voltage was greater than 0.38mV, so
they defined fibrosis voltage threshold in 0.4mV. Other studies have
been carried out in patients with supraventricular tachycardia
undergoing left atrium mapping: Saghy17 established a
cut-point between fibrotic and healthy tissue in 0.5mV in a study of 9
patients, while Yagashita18 proposed 1.17 mV in a
study of 6 patients. In the literature, the most widely used voltage
value is 0.5mV, but it may not be a threshold sensitive enough to
identify areas with arrhythmogenic potential. Several
studies6-11 have assessed the usefulness of an
individualized ablation guided by LVA and most of them have used the
0.5mV threshold. In nearly all of them, LVA ablation has shown
favourable results, what would support, although without great
certainty, that this threshold level may be correct. However, these
studies have important methodological differences, some of them in
mapping that could influence LVA determination. These differences
include mapping catheter electrodes spacing, electrode size, tissue
contact, signal filtering, map’s number of points and heart rhythm
during mapping. In our study we used a multi-electrode catheter with
electrode size of 1 mm2, similar to that used in
Yang19and Jadidi20 studies, while
the rest of studies used larger catheters. In healthy tissue, large
catheters can cause a higher voltage record, whereas in areas with some
fibrosis, a voltage summation of healthy and fibrotic voltages can
result in lower amplitude signals21. Our mapping
catheter, despite not having a direct contact force measurement, does
have a tool that confirms proper contact before signal recording of a
point. Adequate and consistent tissue contact is essential to avoid
underestimation of endocardial signals voltage. Regarding the maps´
number of points, the present work presents the advantage of
high-density mapping. All maps presented more than 400 points, with a
mean number of points in AF maps of 3428 and in SR map of 2319 points,
much higher than average number of points from previous studies (100-200
points) with a maximum in Jadidi’s study22 with 1024
points.
The main strength of our work lies in its objective: comparison of LVA
according to maps’ rhythm. In none of the exposed studies, mapping has
been carried out in both rhythms in the same patient. Our results show
that for a certain voltage threshold, LVA extension is greater in AF
maps than in SR maps. Indeed, for the 0.5mV threshold, the mean area in
AF maps was 41.3 ± 42.5 cm2whereas in SR maps was 11.7
± 17.9 cm2 (p<0.001). For the 0.3 mV
threshold, it was 15.6 ± 22.1 cm2 in AF maps and 6.2 ±
11.5 cm2 in SR maps (p<0.001). Another
finding in the same vein was that the percentage of points below both
thresholds was higher in AF maps than in SR maps. Likewise, the mean
voltage of AF maps was significantly lower than in SR maps (0.62 mV ±
0.27 mV in AF vs. 1.62 ± 0.7 mV in SR, p<0.001). Since
fibrosis is defined histologically and cannot be modified depending on
heart rhythm, these data support that acquisition mapping rhythm implies
a variation in the voltage recorded at each endocardial point. In fact,
as early as 2003, Ndrepepal23 group assessed mean
voltage in the left and the right atrium in SR and AF and observed that
the voltage was significantly reduced when mapping was in AF. In
addition, they observed that areas with the shortest AF length cycle had
a greater voltage difference between AF and SR, suggesting a possible
effect of rapid and disorganized depolarization on collected voltages.
More recently, a Spanish study24 ,carried out with a
very accurate methodology, goes further and compares voltages of
selected points in SR maps and in arrhythmia maps (in some cases AF and
in others atrial flutter). They established that a value of 0.5mV in SR
maps corresponds to 0.38mV in atrial flutter maps and to 0.31 mV in AF
maps. With these data and with those obtained in our work, we consider
that it is necessary to establish different voltage thresholds depending
on the rhythm in which mapping is performed. Furthermore, these
thresholds should be generalized to scientific studies that evaluate LVA
ablation impact. Also, parameters and tools for mapping should be
standardized so they could be properly compared and generalized to
clinical practice in case of favourable results.
Since LVA were less extensive in SR maps, we compared the SR LVA
location to the AF LVA location. The qualitative scale we used did not
allow comparison if there were not LVA areas in SR maps. We checked that
in most of patients, LVA in SR were present in maps in AF. From our
point of view, these data indicate that LVA in SR probably correspond to
fibrosis, but it does not allow us to determine if the 0.5mV threshold
supposes an overestimation of fibrosis zones in AF or an underestimation
of these areas in SR.
In respect of post-ablation clinical evolution, we must emphasize that
our data is only descriptive and exploratory for further investigations.
Despite the fact that statistical significance is not reached in either
of the two type of maps, if we consider LVA as a marker of fibrosis and
therefore as a possible factor influencing post-ablation outcomes, we
found, for the 0.5mV threshold, an almost significant relationship
between recurrences and absolute LVA percentage and LVA percentage
greater than 5% (p=0.06). This does not happen at all with data in SR,
whose results are far from significance. Although not clearly stated, it
is possible that if patient sample had been more numerous, extension of
LVA in AF would have been a factor clearly related to arrhythmic
recurrences in post-ablation follow-up.
LIMITATIONS
It stands out that this is a study with few patients, although its
sample number is similar to many previous publications that address
atrial EAM. Areas in AF and SR were both measured manually, that may
cause operator-dependent variations. However, intraclass correlation
coefficients show adequate inter-operator agreement. Because of this,
this factor influence seems to play a minor role. The study was not
designed and does not have a sufficient sample size to assess
evolutionary data, so obtained results are only exploratory.
CONCLUSION
Using the same voltage thresholds, LVA extension in AF is greater than
in SR for patients with persistent AF. Location of LVA in SR is present
in AF in most of the patients. These findings provide arguments for
defining a different atrial fibrosis threshold based on EAM rhythm.
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